Promising results were observed in a small, prospective study published in JAMA, in which patients with chemotherapy-induced cardiomyopathy (CHIC) were treated with cardiac resynchronization therapy (CRT).1
Certain cytotoxic agents, especially anthracyclines, as well as other anticancer treatments such as some monoclonal antibodies and tyrosine kinase inhibitors, are associated with an increased risk of cardiomyopathy. Termed CHIC, this progressive condition is believed to be due to drug-related myocyte death, resulting in ventricular remodeling, and ultimately leading to heart failure. It can develop years after exposure to these drugs, and is associated with poor clinical outcomes, particularly when left bundle branch block is also present.
Data on the prevention of CHIC are limited, and the use of CRT to treat patients with this condition has not previously been systematically addressed.
This, multicenter, single-arm study, called The Multicenter Automatic Defibrillator Implantation Trial–Chemotherapy-Induced Cardiomyopathy (MADIT-CHIC; ClinicalTrials.gov Identifier: NCT02164721), enrolled cancer survivors with CHIC from 12 tertiary centers with cardio-oncology programs. None of these patients had a history of heart failure prior to cancer treatment or had other underlying causes of cardiomyopathy, and all developed systolic dysfunction 6 months or longer following such treatment.
Two-dimensional echocardiography was performed at baseline and 6 months following implantation of a CRT-defibrillator/pacemaker generator. The primary study end point was change in left-ventricular ejection fraction (LVEF) from baseline to 6 months after initiating CRT.
Of the 30 cancer survivors enrolled in the study, the mean patient age was 64 years. Most patients were women (87%) and white (75%). Cancer history included breast cancer (73%), lymphoma/leukemia (20%), and sarcoma (7%), and cancer-treatment history included anthracycline therapy (83%), cyclophosphamide (10%), trastuzumab (3.3%), dasatinib (3.3%), and docetaxel (3.3%).
The median LVEF at baseline was 29%, all patients had left bundle-branch block, and New York Heart Association (NYHA) class II and class III heart failure was present in 57% and 43% of patients, respectively. The median time between last cancer diagnosis and diagnosis of heart failure was 13.8 years. CRT defibrillators and CRT pacemakers were implanted in 86.7% and 13.3% of patients, respectively.
Of the 26 patients for whom paired echocardiograms were available, the mean LVEF improved from 28% at baseline to 39% at 6 months (P < .001) following implantation of the CRT device. Statistically significant reductions in left ventricular end-systolic and end-diastolic volumes were also observed at 6-month follow-up. No deaths occurred during the study and only 1 heart failure event was reported. Pneumothorax and a device pocket infection each occurred in 1 patient.
In speculating on these results, the study authors noted that “the primary benefit of CRT in this cohort of patients could be due to the direct reversal of mechanical dys-synchrony and the associated improved remodeling of the heart.”
Limitations of the study, identified by the study authors and the authors of an accompanying editorial, included its small size, short follow-up period, no control arm, and the use of 2-dimensional, rather than 3-dimensional, echocardiography.1,2
It was further noted that the small study size may itself be an indicator of an unmet need with respect to the identification of patients at risk of heart failure following receipt of cardiotoxic therapies, and that “the adult cardiology and oncology communities need a more harmonized approach to cardiovascular care of patients with cancer.”1,2
- Singh JP, Solomon SD, Fradley MG, et al. Association of cardiac resynchronization therapy with change in left ventricular ejection fraction in patients with chemotherapy-induced cardiomyopathy. JAMA. 2019;322:1799-1805.
- Meijers WC, Moslehi JJ. Need for multidisciplinary research and data-driven guidelines for the cardiovascular care of patients with cancer. JAMA.2019;322:1775-1776.